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Biological & Pharmaceutical Bulletin 2024Patients with hematological malignancies (HM) often receive tazobactam/piperacillin (TAZ/PIPC) and glycopeptide antibiotics for febrile neutropenia. The effect of... (Observational Study)
Observational Study
Patients with hematological malignancies (HM) often receive tazobactam/piperacillin (TAZ/PIPC) and glycopeptide antibiotics for febrile neutropenia. The effect of concomitant use of TAZ/PIPC on risk of teicoplanin (TEIC)-associated acute kidney injury (AKI) remains unclear. We investigated the impact of concomitant TAZ/PIPC use on TEIC-associated AKI in HM patients and identified the risk factors. In this retrospective, single-center, observational cohort study, 203 patients received TEIC, 176 of whom satisfied the selection criteria and were divided into TEIC cohort (no TAZ/PIPC; n = 118) and TEIC + TAZ/PIPC cohort (n = 58). AKI was defined as serum creatinine increase ≥0.3 mg/dL within 48 h or ≥50% from baseline. Incidence of AKI in TEIC cohort before and after propensity score matching was 9.3 and 5.9%, respectively, and that in TEIC + TAZ/PIPC cohort was 10.3 and 11.8%. AKI incidence and risk were not significantly different between two cohorts before (p = 0.829; odds ratio (OR) 1.122, 95% confidence interval (CI) 0.393-3.202) and after matching (p = 0.244; OR 2.133, 95% CI 0.503-9.043). Logistic regression analysis with factors clinically or mechanistically potentially related to TEIC-associated AKI, including concomitant TAZ/PIPC use, as independent variables identified baseline hemoglobin level as the only significant risk factor for TEIC-associated AKI (p = 0.011; OR 0.484, 95% CI 0.276-0.848). In HM patients treated with TEIC, concomitant TAZ/PIPC use did not increase AKI risk whereas lower hemoglobin levels had higher risk for TEIC-associated AKI development, suggesting the necessity to monitor serum creatinine when using TEIC in patients with anemia.
Topics: Humans; Acute Kidney Injury; Male; Teicoplanin; Female; Middle Aged; Hematologic Neoplasms; Piperacillin, Tazobactam Drug Combination; Risk Factors; Anti-Bacterial Agents; Retrospective Studies; Aged; Adult
PubMed: 38763761
DOI: 10.1248/bpb.b23-00848 -
International Journal of Molecular... Apr 2024Due to the favorable features obtained through the incorporation of fluorine atom(s), fluorinated drugs are a group with emerging pharmaceutical importance. As their...
Liquid Chromatographic Enantioseparation of Newly Synthesized Fluorinated Tryptophan Analogs Applying Macrocyclic Glycopeptides-Based Chiral Stationary Phases Utilizing Core-Shell Particles.
Due to the favorable features obtained through the incorporation of fluorine atom(s), fluorinated drugs are a group with emerging pharmaceutical importance. As their commercial availability is still very limited, to expand the range of possible candidates, new fluorinated tryptophan analogs were synthesized. Control of enantiopurity during the synthesis procedure requires that highly efficient enantioseparation methods be available. In this work, the enantioseparation of seven fluorinated tryptophans and tryptophan was studied and compared systematically to (i) develop analytical methods for enantioselective separations and (ii) explore the chromatographic features of the fluorotrytophans. For enantioresolution, macrocyclic glycopeptide-based selectors linked to core-shell particles were utilized, applying liquid chromatography-based methods. Application of the polar-ionic mode resulted in asymmetric and broadened peaks, while reversed-phase conditions, together with mobile-phase additives, resulted in baseline separation for all studied fluorinated tryptophans. The marked differences observed between the methanol and acetonitrile-containing eluent systems can be explained by the different solvation abilities of the bulk solvents of the applied mobile phases. Among the studied chiral selectors, teicoplanin and teicoplanin aglycone were found to work effectively. Under optimized conditions, baseline separations were achieved within 6 min. Ionic interactions were semi-quantitatively characterized and found to not influence enantiorecognition. Interestingly, fluorination of the analytes does not lead to marked changes in the chromatographic characteristics of the methanol-containing eluents, while larger differences were noticed when the polar but aprotic acetonitrile was applied. Experiments conducted on the influence of the separation temperature indicated that the separations are enthalpically driven, with only one exception. Enantiomeric elution order was found to be constant on both teicoplanin and teicoplanin aglycone-based chiral stationary phases ( < ) under all applied chromatographic conditions.
Topics: Tryptophan; Glycopeptides; Stereoisomerism; Teicoplanin; Halogenation; Chromatography, Liquid; Chromatography, High Pressure Liquid; Macrocyclic Compounds
PubMed: 38731937
DOI: 10.3390/ijms25094719 -
Cureus Dec 2023Hospital-acquired pneumonia (HAP) is a life-threatening hospital-acquired infection contributing to poor outcomes and mortality. Though the prevalence is...
BACKGROUND AND OBJECTIVES
Hospital-acquired pneumonia (HAP) is a life-threatening hospital-acquired infection contributing to poor outcomes and mortality. Though the prevalence is comparable, the burden of comorbidities and malnutrition further worsens the scenario in developing countries. Infective agents responsible for these infections vary between regions due to the variables involved. There is a dearth of data on clinico-microbiological correlates of HAP from Northern India. With this study, we aim to explore the same and add more evidence to fill the gap.
METHODOLOGY
A hospital-based cohort study was done on ICU patients of the tertiary care center in Northern India including the cohort of patients obeying a strict inclusion criterion. The clinical and microbiological correlates were estimated following an appraisal of quality of study samples.
RESULTS
We found that the most common clinical feature in patients with HAP was fever (82%) followed by purulent respiratory secretions (72%), tachycardia (52%), and crepitations on auscultation (38%). Approximately 86% of cases were found to be culture-positive while others were bacteriologically sterile. Gram-negative bacilli were more commonly isolated (83% Gram-negative vs 17% Gram-positive). The most common organisms isolated were Klebsiella pneumoniae, Citrobacter freundii, Escherichia coli, Acinetobacter, and Pseudomonas aeruginosa. Staphylococcus aureus was isolated from eight specimens and all isolates were susceptible to vancomycin, linezolid, teicoplanin, and tigecycline. Seven isolates were resistant to clindamycin and all 8 were resistant to macrolides and quinolones. Five strains had methicillin resistance indicating a rising burden of 'superbugs'. The most common side involved was the right side and the right middle zone was the most common zone involved. Forty-four percent of cases had a poor outcome and succumbed to the infection.
CONCLUSIONS
HAP places patients at a heightened risk of mortality and manifests a distinctive clinical-microbiological profile. It is advisable to adopt a proactive stance in averting HAI by adhering to robust prophylaxis and management protocols in alignment with regional data and hospital guidelines. Despite the study's constrained sample size, it contributes significant insights specific to the region. This underscores the necessity for further exploration through analogous studies and audits in the northern part of India. Such endeavors have the potential to tailor treatment approaches for patients, ultimately enhancing overall outcomes.
PubMed: 38694727
DOI: 10.7759/cureus.50707 -
Cureus Mar 2024Coagulase-negative staphylococci (CoNS) are one of the frequently isolated bacteria from blood cultures. Since they are part of the normal skin flora, they were...
BACKGROUND
Coagulase-negative staphylococci (CoNS) are one of the frequently isolated bacteria from blood cultures. Since they are part of the normal skin flora, they were previously considered contaminants. But now, they can be considered as established pathogens causing bloodstream infection (BSI). This study aims to estimate the prevalence of CoNS in BSI cases.
METHODS
This study was conducted at the Microbiology Department, All India Institute of Medical Sciences (AIIMS), Raipur, India, for eight months (January 2022 to August 2022). Data were collected retrospectively from medical and laboratory records. Paired blood cultures from 5085 clinically suspected sepsis cases were subjected to aerobic culture for five days in the BacT ALERT 3D system. Pathogenicity was established after recovery of CoNS from paired blood cultures of symptomatic patients.
RESULTS
CoNS were isolated from 2.35% of patients, the most common species being (51.67%). About 90% of isolates were methicillin-resistant. All the isolates were susceptible to linezolid, teicoplanin, and vancomycin, except one isolate of which was intermediate to vancomycin. Minimum inhibitory concentration (MIC) 50 and MIC 90 for vancomycin were 1 ug/ml and 2 ug/ml, respectively. Conclusion: Paired blood cultures are necessary to determine the pathogenicity of CoNS in BSI cases. A high prevalence of methicillin resistance, accompanied by high resistance rates to other non-beta lactam antibiotics, warrants the strict implementation of antimicrobial stewardship practices.
PubMed: 38686262
DOI: 10.7759/cureus.57250 -
Infection and Drug Resistance 2024Lymphoma is complicated by intricate infections, notably pneumonia (PJP), marked by rapid progression, respiratory failure, and high mortality. Rapid diagnosis of PJP...
BACKGROUND
Lymphoma is complicated by intricate infections, notably pneumonia (PJP), marked by rapid progression, respiratory failure, and high mortality. Rapid diagnosis of PJP and effective administration of the first-line treatment trimethoprim-sulfamethoxazole (TMP-SMX) are important. For patients intolerant to TMP-SMX, selecting appropriate alternatives is challenging, necessitating careful decisions to optimize diagnosis and treatment. We present a lymphoma case complicated by PJP, illustrating medication adjustment until a positive response was observed.
CASE DESCRIPTION
A 41-year-old male patient with lymphoma presented with a week-long history of fever, fatigue, cough, sputum, chest tightness, and exertional dyspnea, unresponsive to treatment. Routine laboratory examinations revealed no pathogenic bacteria. PJ and (MTB) were detected in bronchoalveolar lavage fluid (BALF) using metagenomic next-generation sequencing (mNGS). On Day 1 of admission, meropenem, TMP-SMX, and rifampicin+isoniazid+levofloxacin were administered. However, the patient developed drug-induced hepatotoxicity and gastrointestinal adverse reactions after six days of treatment. After a multidisciplinary team discussion, anti-tuberculosis therapy was stopped because of insufficient evidence of tuberculosis infection. A reduced dose of TMP-SMX with micafungin was used for PJP; however, symptoms persisted and repeated computed tomography showed extensive deterioration of bilateral pulmonary plaques. The PJP regimen was modified to include a combination of TMP-SMX and caspofungin. Due to the high fever and elevated infection indices, the patient was treated with teicoplanin to enhance the anti-infection effects. By Day 13, the patient's temperature had normalized, and infection control was achieved by Day 30. CT revealed that the infection in both lung lobes fully resolved. Subsequently, lymphoma treatment commenced.
CONCLUSION
BALF-NGS facilitates early and rapid diagnosis of PJP. mNGS reads of MTB bacillus <5 may indicate a bacterial carrier state, warranting other detection techniques to support it. There is insufficient evidence for using TMP-SMX with micafungin to treat PJP; however, TMP-SMX combined with caspofungin is suitable.
PubMed: 38681899
DOI: 10.2147/IDR.S461607 -
Mikrobiyoloji Bulteni Apr 2024The aim of this study was to investigate the detection of teicoplanin and fosfomycin antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA)...
[Investigation of the Antibacterial Synergistic Activity of Fosfomycin-Teicoplanin Combination in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Various Clinical Sample].
The aim of this study was to investigate the detection of teicoplanin and fosfomycin antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains by different methods and to evaluate the antibacterial synergistic effect of teicoplanin-fosfomycin combination by using checkerboard assay and time kill curve assay. Forty-five MRSA strains isolated from clinical samples in routine medical microbiology laboratory of Göztepe Prof. Dr. Süleyman Yalçın City Hospital were included in the study. In the first stage of the combination study, minimum inhibitory concentrations (MIC) were investigated by broth microdilution for teicoplanin and by both broth microdilution and agar dilution methods for fosfomycin. The combination of teicoplanin and fosfomycin was tested by the checkerboard method in 45 MRSA strains and combination effect was determined according to fractional inhibitory concentration index (ΣFIC) calculation. The synergistic effect and bactericidal activity of antibiotic combination were studied against a randomly selected strain from the strains used in the study by using time-kill method for 24 hours. As a result of teicoplanin and fosfomycin antibiotic susceptibility studies, all isolates were found to be susceptible to both antibiotics according to the susceptibility breakpoints determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A synergistic effect was found in 22 (49%), additive effect in 22 (49%) and indifferent effect in one (2%) of the 45 strains studied with the checkerboard method. The mean ΣFIC of 45 isolates was found to be 0.5. In the combination study of the antibiotics of the isolate that was studied with time-kill method, synergism was detected for 1/8 MIC concentrations at 12th hour and 24th hour and synergism at 1/4 MIC concentration at sixth hour, 12th hour and 24th hour. In the combination study of 1/4 MIC concentrations of antibiotics, bactericidal effect was detected at sixth hour and this effect was observed to disappear at 12th and 24th hours. High rate of synergistic antibacterial effect of teicoplanin-fosfomycin combination on MRSA isolates was demonstrated as a result of in vitro tests. Such studies conducted on antibiotic-resistant bacterial infections will provide clinicians different treatment options and will contribute to increasing survival. As a result of this study, provided that it is supported by future clinical studies, it can be stated that the teicoplanin-fosfomycin combination may be an effective treatment option in community and hospital-acquired infections caused by MRSA.
Topics: Fosfomycin; Methicillin-Resistant Staphylococcus aureus; Teicoplanin; Microbial Sensitivity Tests; Drug Synergism; Anti-Bacterial Agents; Humans; Staphylococcal Infections
PubMed: 38676580
DOI: 10.5578/mb.202498156 -
Pharmaceuticals (Basel, Switzerland) Mar 2024We aimed to determine the trend of the antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit...
We aimed to determine the trend of the antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU) in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. Positive bacterial culture data from 1695 samples from the pre-COVID-19 period and 1562 samples from the post-COVID-19 period were obtained. The most frequently isolated bacteria in both periods were and spp. The resistance rates of spp. Significantly increased against colistin (0.38% to 20.51%), gentamicin (44.62% to 64.85%), and aztreonam (56.35% to 3.60%). There was a significant increase in the resistance rate against colistin for strains (4.69% to 32.46%) and for Acinetobacter sp. strains (3.37% to 18.09%). More than 50% of the strains were MRSA, with statistically significant increases in the antimicrobial resistance rate against doxycycline (40.08% to 51.72%), linezolid (0.22% to 3.13%), rifampicin (53.16% to 64.93%), and teicoplanin (26.31% to 53.40%). The study revealed a significantly increasing trend in the antimicrobial resistance rate of Gram-negative pathogens against certain antibiotics, including those used only in cases where there are no other therapeutic options.
PubMed: 38675369
DOI: 10.3390/ph17040407 -
Pharmaceutics Apr 2024In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model...
In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.
PubMed: 38675160
DOI: 10.3390/pharmaceutics16040499 -
Antibiotics (Basel, Switzerland) Mar 2024Vancomycin is the cornerstone in treating methicillin-resistant (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased...
Vancomycin is the cornerstone in treating methicillin-resistant (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro -tests. Suspicious hVISA were studied by population analysis profiling-area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCC IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.
PubMed: 38666974
DOI: 10.3390/antibiotics13040298 -
Heliyon Apr 2024affects elderly people and is associated with individuals with urological-related predispositions, but can be found in a variety of locations, such as cutaneous,...
affects elderly people and is associated with individuals with urological-related predispositions, but can be found in a variety of locations, such as cutaneous, intraabdominal, genitourinary and surgical infections. Disseminated infections occur less frequently and are by and large related to urinary tract colonisation. This pathogen is often neglected due to growth requirements, especially in urinary tract infections. We present 107 isolated from genitourinary samples (80.4%), from skin and soft tissue infections (13.1%), from bone and deep tissue infection (4.7%) and from blood cultures (1.9%). The automated system Alfred 60/AST was paramount for the isolation of 77.6% of the UTI. All the isolates tested were susceptible to penicillin, ampicillin, linezolid, vancomycin, teicoplanin, rifampicin and tetracycline. In conclusion, we present a large series of infections. This pathogen is hard to isolate, and is resistant to commonly used empirical antimicrobials.
PubMed: 38590897
DOI: 10.1016/j.heliyon.2024.e28589